A study conducted by researchers at UCLA Health Johnsson Comprehensive Cancer Center in Los Angeles, CA, MD Anderson Cancer Center in Houston, TX, and Sloan Kettering Cancer Center in New York found that a cancer vaccine candidate called ELI-002 2P elicited a strong immune response in patients with colorectal and pancreatic cancer.
The study, published earlier this month in Nature Medicine, included the results from the phase 1 AMPLIFY-201 trial, which evaluated the safety and efficacy of ELI-002 2P, a lymph node-directed vaccine targeting KRAS mutations. These types of mutations occur in approximately 25% of solid tumors, including 50% of colorectal cancers and 93% of pancreatic cancers.
The ELI-002 2P vaccine candidate, developed by Boston-based Elicio Therapeutics, uses an amphiphile technology to direct antigens directly to the lymph nodes that activate immune responses. The vaccine is designed as an off-the-shelf product meant to recognize and target cancer cells in a general manner, avoiding the need for tumor-specific, personalized vaccines.
The study included 25 patients with colorectal cancer or pancreatic ductal adenocarcinoma who had undergone standard tumor treatment and showed minimal residual mutant KRAS disease. The participants received a series of subcutaneous injections with ELI-002 2P and were followed for a median of 19.7 months.
The research team, led by Zev A. Wainberg, M.D., professor of medicine at UCLA, found that 84% of the patients developed both CD4+ helper and CD8+ killer T cells targeting mutant KRAS. Furthermore, in 24% of participants, tumor-associated biomarkers were completely cleared. Of the patients who showed the strongest immune response, the majority (71%) were cancer-free almost 20 months later.
Among all participants, the median relapse-free survival was 16.33 months, and the median overall survival was 28.94 months. Both figures exceeded the expected survival rates for these types of cancer. Wainberg and his colleagues also found that 67% of patients elicited immune responses to other cancer-driving mutations.
Additional analyses shed more light on why some patients responded better than others. The researchers identified a threshold level of T-cell activation—defined as a 9.17-fold increase from baseline—that separated patients with more favorable outcomes. Those above the threshold showed dramatic benefits. For example, none had radiographic progression during follow-up, and their median overall survival had not yet been reached. In addition, nearly all patients below the threshold experienced relapse or death, highlighting the importance of achieving strong T-cell expansion. The vaccine also appeared to promote “antigen spreading,” where immune responses broadened beyond KRAS to attack other tumor neoantigens.
These results were observed in about two-thirds of tested patients, suggesting a more durable and diversified antitumor effect. Researchers noted that these results are especially striking given the historically poor outcomes for pancreatic cancer, where standard therapy alone often leads to rapid relapse.
The findings support further testing of ELI-002 not only as a stand-alone treatment but also in combination with other therapies such as checkpoint inhibitors. Future studies may determine whether giving the vaccine earlier, when tumor burden is low, provides even greater benefit.
A larger phase 2 trial is underway evaluating the safety and efficacy of ELI-002 7P, an expanded version of ELI-002 2P targeting a broader range of KRAS mutations.